Evaluation of an Adoptive Cellular Therapy-Based Vaccine in a Transgenic Mouse Model of α-synucleinopathy

Aggregated alpha-synuclein, a major constituent of Lewy bodies plays a crucial role in the pathogenesis of alpha-synucleinopathies (SPs) such as Parkinson's disease (PD). PD is affected by the innate and adaptive arms of the immune system, and recently both active and passive immunotherapies targeted against alpha-synuclein (alpha-syn) are being developed and show promise as novel treatment strategies for such diseases. Specifically, dendritic cell-based vaccines have shown to be an effective treatment for SPs. Here, we report on the development of adoptive cellular therapy (ACT) for SP and demonstrate that adoptive transfer of pre-activated T-cells generated from immunized mice can improve survival and behavior, reduce brain microstructural impair-ment via magnetic resonance imaging (MRI), and decrease alpha-synuclein pathology burden in a peripherally induced preclinical SP model (M83) when administered prior to disease onset. This study provides evidence for ACT as a candidate immunotherapy for other forms of SPs.

Automated summary

This study reports on the development of adoptive cellular therapy (ACT) targeted against alpha-synucleinopathies (SPs) and demonstrates its effectiveness in a preclinical SP model. The adoptive transfer of pre-activated T-cells generated from immunized mice improves survival, behavior, brain microstructural impairment, and reduces alpha-synuclein pathology burden. This study provides evidence for ACT as a candidate immunotherapy for other forms of SPs.